Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 44, Issue 2, Pages 539-543Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41366-019-0428-7
Keywords
-
Categories
Funding
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
- French National Research Agency [ANR-10-LABX46, ANR-10-EQPX-0701]
- European Research Council [ERC GEPIDIAB-294785, ERC Reg-Seq-715575]
- FEDER
- Region Nord Pas-de-Calais
- Inserm
- Caisse nationale de l'assurance maladie des travailleurs salaries
- Lilly
- Novartis Pharma
- SanofiAventis
- Inserm (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR 2008)
- Association Diabete Risque Vasculaire
- Federation Francaise de Cardiologie
- La Fondation de France
- Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques/Societe Francophone de Diabetologie
- Office national interprofessionnel des vins
- Ardix Medical
- Bayer Diagnostics
- Becton Dickinson
- Cardionics
- Merck Sante
- Novo Nordisk
- Pierre Fabre
- Roche
- Topcon
Ask authors/readers for more resources
Background Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for understanding how these genetic loci physiologically impact disease development. Methods We performed a PCR-free expression assay targeting genes located nearby the GWAS-identified SNPs associated with BMI/obesity in a large panel of human tissues. Furthermore, we analyzed several genetic risk scores (GRS) summing GWAS-identified alleles associated with increased BMI in 4236 individuals. Results We found that the expression of BMI/obesity susceptibility genes was strongly enriched in the brain, especially in the insula (p = 4.7 x 10(-9)) and substantia nigra (p = 6.8 x 10(-7)), which are two brain regions involved in addiction and reward. Inversely, we found that top obesity/BMI-associated loci, including FTO, showed the strongest gene expression enrichment in the two brain regions. Conclusions Our data suggest for the first time that the susceptibility genes for common obesity may have an effect on eating addiction and reward behaviors through their high expression in substantia nigra and insula, i.e., a different pattern from monogenic obesity genes that act in the hypothalamus and cause hyperphagia. Further epidemiological studies with relevant food behavior phenotypes are necessary to confirm these findings.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available